The cloning of the mouse obesity gene (ob) has revived interest in the factors regulating body weight. The ob gene encodes an adipose tissue derived protein (leptin) which seems to act centrally to regulate food intake and energy expenditure. The recent identification and cloning of the leptin receptor (which is highly expressed in the central nervous system, especially the choroid plexus and hypothalamus) has offered some possible explanation of how leptin can be transported from the plasma to cerebrospinal fluid. Since no defect in leptin production has been described in obese humans, we hypothesize that the transport of leptin from the plasma to the CSF is impaired in obesity prone subjects. In this project leptin concentrations will be measured in the plasma and in the CSF in 20 subjects (10 Pima Indians and 10 non-Pima Indians, matched for age, gender, and body mass index) and will be related to measures of body composition (dual energy X-ray absorptiometry) and 24-hour energy expenditure (respiratory chamber).